Transgenic mice are reported to develop diabetes at a similar or higher rate and kinetics as wildtype controls. Transgenic mice may be useful in studies of diabetes and pancreatic beta islet cell biology. NOD mice are used as an animal model for type 1 diabetes. NOD mice exhibit a susceptibility to spontaneous development of autoimmune insulin dependent diabetes mellitus (IDDM). Genetic Loci associated with susceptibility to IDDM have been identified in the NOD mouse strain through the development of congenic mouse strains, which have identified several insulin dependent diabetes (Idd) loci. In view of the fact that the NOD mice' unique genetic factors and pathological mechanism are similar to human type 1 diabetes, NOD mice are an important animal model in exploring IDDM mechanism and evaluating various therapeutic strategies.
However, to explore whether apoptosis progresses in pancreatic beta-cells (insulitis), a number of NOD mice should be sacrificed to obtain a series of pancreas islet sections at continuous time points. As a result, researches cannot continuously observe pathological process in one mouse and use the method of monitoring blood sugar of NOD mice to evaluate progress of diabetes; only late-stage diabetes can be measured. Moreover, the incidence of spontaneous diabetes in the NOD mouse is 60-80% in females and 20-30% in males. Onset of diabetes also varies between males and females: commonly, onset is delayed in males by several weeks. Therefore, the variations in animal gender and environmental and experimental conditions would impact the research results of diabetes. For example, NOD.Cg-Tg (Ins1-EGFP)1Hara/QtngJ (also known as: MIP-GFP (line 1), NOD.B6-MIP-GFP) is a congenic NOD mouse ice hemizygous for the MIP-GFP transgene, which has EGFP fluorescence in tissues where insulin I is normally detected, specifically in pancreatic beta-cells. However, this NOD transgenic mouse only can be used in optical imaging system and the observation on diabetes can be performed only after the mouse is sacrificed. Moreover, the GFP originated from jellyfish may cause immune rejection when the pancreatic islets of NOD mouse are transplanted to normal mouse. U.S. Pat. No. 8,507,207 provides a reporter gene system, and in particular relates to a method for using a recombinant nucleotide sequence encoding an anti-polyethylene glycol recombinant single chain membrane antibody as a reporter gene to monitor presence and distribution of a gene and a cell.
However, there is a need to develop a NOD mouse that can be used in continuous observation of diabetes pathological process and evaluation of drug treatment of type I diabetes.